Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
A naturally occurring Vif mutant (I107T) attenuates anti-APOBEC3G activity and HIV-1 replication
Journal of Molecular Biology, Volume 425, No. 16, Year 2013
Notification
URL copied to clipboard!
Description
The human immunodeficiency virus type 1 (HIV-1) Vif protein counteracts the antiviral activity of the apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) family of proteins by targeting the proteins for degradation through the ubiquitin-proteasome pathway. Previous mutagenic studies have shown that multiple domains of Vif are required for interacting with APOBEC3G proteins and the proteasome pathway. However, very few mutagenesis and functional analyses of patient-derived Vif proteins have been conducted. In this study, we amplified and cloned the HIV-1 vif genes from the peripheral blood mononuclear cells (PBMCs) of five HIV-1-infected individuals in Nairobi and further tested the impact of the genes on anti-A3G activity and HIV-1 replication. The gene sequence analysis revealed high genetic variation of vif genes from different HIV-1-infected individuals. Interestingly, the Vif proteins derived from two of the three long-term survivors (LTSs) displayed a significantly impaired ability to mediate the degradation of A3G. In particular, a single amino acid change (I107T) in one of the non-functional LTS Vif variants, which has not been previously identified in the Los Alamos databases of vif sequences, was found to be responsible for the lack of anti-A3G activity. Further study demonstrated that HIV-1 carrying an I107T Vif mutation displayed significantly reduced fitness in A3G+ T cells and PBMCs. Moreover, co-infecting A3G+ T cells with both the wild-type and I107T Vif viruses resulted in decreased viral replication. Overall, the results of this study indicate that the HIV-1 Vif residue I107 is important for its anti-APOBEC3G activity and viral replication, which may have implications for viral fitness in vivo. © 2013 Elsevier Ltd.
Authors & Co-Authors
Ao, Zhujun
Canada, Winnipeg
University of Manitoba
Ramdahin, Sue G.
Canada, Winnipeg
University of Manitoba
Chen, Xi
Unknown Affiliation
Ball, Terry Blake
Canada, Winnipeg
University of Manitoba
China, Changsha
Central South University
Fowke, Keith Raymond
Unknown Affiliation
Plummer, Francis Allan
Canada, Winnipeg
University of Manitoba
Embreé, Joanne E.
Canada, Winnipeg
University of Manitoba
Yao, Xiaojian
Canada, Winnipeg
University of Manitoba
Statistics
Citations: 10
Authors: 8
Affiliations: 2
Identifiers
Doi:
10.1016/j.jmb.2013.05.015
ISSN:
00222836
Research Areas
Cancer
Genetics And Genomics
Health System And Policy
Infectious Diseases